匹妥布替尼在大鼠体内的代谢产物鉴定及代谢途径分析  

Metabolite identification and metabolic pathway analysis of pirtobrutinib in rats

作　　者：张美娟 李洁[2] 尹航[1] 侯梦雨 李江硕 吴竞轩 董瑞华 ZHANG Meijuan;LI Jie;YIN Hang;HOU Mengyu;LI Jiangshuo;WU Jingxuan;DONG Ruihua(Dept.of Research Ward,Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China;School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China)

机构地区：[1]首都医科大学附属北京友谊医院研究型病房,北京100050 [2]北京中医药大学中药学院,北京102488

出　　处：《中国药房》2025年第9期1076-1081,共6页China Pharmacy

基　　金：首都卫生发展科研专项(No.首发2022-2Z-20215)。

摘　　要：目的分析、鉴定匹妥布替尼(PTN)在大鼠体内的代谢产物,并探讨其在大鼠体内的可能代谢途径。方法6只大鼠按照10 mg/kg灌胃PTN混悬液,收集大鼠给药前30 min以及给药后0.25、0.5、1、2、4、6、8、12、24 h的血液和给药前12 h及给药后24 h的尿液和粪便。采用UHPLC-Orbitrap Exploris 240系统联合Compound Discoverer 3.0和Xcalibur 2.0数据分析软件对PTN在大鼠血浆、尿液和粪便中的代谢产物进行结构鉴定与代谢途径分析。结果在大鼠生物样本中共鉴定出29种PTN代谢产物,在血浆、尿液和粪便样本中分别鉴定出17、19和22种代谢产物。PTN的代谢途径主要包括氧化、硫酸化、葡萄糖醛酸化等,且其代谢产物多为2种及以上不同代谢形式的组合产物。其中,涉及Ⅰ相代谢反应的产物共计26个(氧化14个、还原/脱氢9个、脱甲基8个、水解5个),涉及Ⅱ相代谢反应的产物共计20个(硫酸化14个、葡萄糖醛酸化8个)。结论PTN在大鼠粪便样本中代谢产物种类较多,主要代谢途径为氧化、硫酸化、葡萄糖醛酸化等。OBJECTIVE To analyze and identify the metabolites of pirtobrutinib(PTN)in rats,and clarify the possible metabolic pathways of PTN in rats.METHODS Six rats were intragastrically administered with 10 mg/kg PTN suspension.Blood samples were collected from the rats 30 minutes before administration and at 0.25,0.5,1,2,4,6,8,12,24 hours after administration.Urine and feces samples were collected 12 hours before administration and 24 hours after administration.UHPLCOrbitrap Exploris 240 system combined with Compound Discoverer 3.0 and Xcalibur 2.0 software were adopted for structural identification and metabolic pathway analysis of PTN metabolites in rat plasma,urine,and feces.RESULTS A total of 29 PTN metabolites were identified,including 17,19 and 22 metabolites in plasma,urine and feces,respectively.The metabolic pathways of PTN mainly included oxidation,sulfation,glucuronidation,etc.,and its metabolites were mostly combination products of two or more different metabolic forms.In detail,a total of 26 metabolites were associated with phaseⅠmetabolic reactions(14 oxidation metabolites,9 reduction/dehydrogenation metabolites,8 demethylation metabolites,and 5 hydrolysis metabolites).Meanwhile,a total of 20 products were involved in phaseⅡmetabolites(14 sulfation metabolites and 8 glucuronic acid binding metabolites).CONCLUSIONS PTN exhibits a diverse range of metabolites in rat fecal samples,with the primary metabolic pathways being oxidation,sulfation,glucuronidation,and others.

关 键 词：匹妥布替尼 代谢产物 代谢途径 

分 类 号：R969.1[医药卫生—药理学] R917[医药卫生—药学]